Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/121088
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Type: Journal article
Title: Sortilin inhibits amyloid pathology by regulating non-specific degradation of APP
Author: Ruan, C.S.
Liu, J.
Yang, M.
Saadipour, K.
Zeng, Y.Q.
Liao, H.
Wang, Y.J.
Bobrovskaya, L.
Zhou, X.F.
Citation: Experimental Neurology, 2018; 299(Pt A):75-85
Publisher: Elsevier
Issue Date: 2018
ISSN: 0014-4886
1090-2430
Statement of
Responsibility: 
Chun-Sheng Ruan, Jia Liu, Miao Yang, Khalil Saadipour, Yue-Qin Zeng, Hong Liao, Yan-Jiang Wang, Larisa Bobrovskaya, Xin-Fu Zhou
Abstract: Amyloid plaque is one of the hallmarks of Alzheimer's disease (AD). The key component beta-amyloid (Aβ) is generated via proteolytic processing of amyloid precursor protein (APP). Sortilin (encoded by the gene Sort1) is a vacuolar protein sorting 10 protein domain-containing receptor, which is up-regulated in the brain of AD, colocalizes with amyloid plaques and interacts with APP. However, its role in amyloidogenesis remains unclear. In this study, we first found that the protein level of sortilin was up-regulated in the neocortex of aged (7 and 9months old) but not young (2 and 5months old) AD mice (APP/PS1). 9months old APP/PS1 transgenic mice with Sort1 gene knockout showed increased amyloid pathology in the brain; and this phenotype was rescued by intrahippocampal injection of AAV-hSORT1. Moreover, the 9months old APP/PS1 mice without Sort1 also displayed a decreased number of neurons and increased astrocyte activation in the hippocampus. In addition, the present study showed that the intracellular domain of sortilin was involved in the regulation of the non-specific degradation of APP. Together, our findings indicate that sortilin is a beneficial protein for the reduction of amyloid pathology in APP/PS1 mice by promoting APP degradation.
Keywords: Sortilin; APP; amyloid production; degradation
Rights: © 2017 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.expneurol.2017.10.018
Grant ID: http://purl.org/au-research/grants/nhmrc/1021408
http://purl.org/au-research/grants/nhmrc/1020567
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